ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis

作者：Anbin Wang, Haisu Dai, Yi Gong, Chengcheng Zhang, Junjie Shu, Yuandeng Luo, Yan Jiang, Wei Liu, Ping Bie · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2019 · DOI：10.1186/s13046-019-1340-7 · 被引用次数：150 · 研究领域：Cardiomyopathy and Myosin Studies、Microtubule and mitosis dynamics、Connective tissue disorders research

BACKGROUND: Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. METHODS: The expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression. RESULTS: We found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregula...